Saturday, November 29, 2014

Chronic pain represents an immense clinical problem. With tens of millions of people in the United States alone suffering from the burden of debilitating chronic pain, there is a moral obligation to reduce this burden by improving the understanding of pain and treatment mechanisms, developing new therapies, optimizing and testing existing therapies, and improving access to evidence-based pain care. Here, we present a goal-oriented research agenda describing the American Pain Society's vision for pain research aimed at tackling the most pressing issues in the field.

Perspective

This article presents the American Pain Society's view of some of the most important research questions that need to be addressed to advance pain science and to improve care of patients with chronic pain.

Nerve cells that transmit pain, itch and other sensations to the brain have been made in the lab for the first time. Researchers say that the cells will be useful for developing new painkillers and anti-itch remedies, as well as understanding why some people experience unexplained extreme pain and itching.

"The short take-home message would be 'pain and itch in a dish', and we think that's very important," says Kristin Baldwin, a stem-cell scientist at the Scripps Research Institute in La Jolla, California, whose team converted mouse and human cells called fibroblasts into neurons that detect sensations such as pain, itch or temperature1. In a second paper2, a separate team took a similar approach to making pain-sensing cells. Both efforts were published on 24 November in Nature Neuroscience.

Thursday, November 27, 2014

In research published in the medical journal Brain, Saint Louis University researcher Daniela Salvemini, Ph.D. and colleagues within SLU, the National Institutes of Health (NIH) and other academic institutions have discovered a way to block a pain pathway in animal models of chronic neuropathic pain including pain caused by chemotherapeutic agents and bone cancer pain suggesting a promising new approach to pain relief.

The scientific efforts led by Salvemini, who is professor of pharmacological and physiological sciences at SLU, demonstrated that turning on a receptor in the brain and spinal cord counteracts chronic nerve pain in male and female rodents. Activating the A3 receptor -- either by its native chemical stimulator, the small molecule adenosine, or by powerful synthetic small molecule drugs invented at the NIH -- prevents or reverses pain that develops slowly from nerve damage without causing analgesic tolerance or intrinsic reward (unlike opioids).

An Unmet Medical Need

Pain is an enormous problem. As an unmet medical need, pain causes suffering and comes with a multi-billion dollar societal cost. Current treatments are problematic because they cause intolerable side effects, diminish quality of life and do not sufficiently quell pain.

The most successful pharmacological approaches for the treatment of chronic pain rely on certain "pathways": circuits involving opioid, adrenergic, and calcium channels.

For the past decade, scientists have tried to take advantage of these known pathways -- the series of interactions between molecular-level components that lead to pain. While adenosine had shown potential for pain-killing in humans, researchers had not yet successfully leveraged this particular pain pathway because the targeted receptors engaged many side effects.

A Key to Pain Relief

In this research, Salvemini and colleagues have demonstrated that activation of the A3 adenosine receptor subtype is key in mediating the pain relieving effects of adenosine.

"It has long been appreciated that harnessing the potent pain-killing effects of adenosine could provide a breakthrough step towards an effective treatment for chronic pain," Salvemini said. "Our findings suggest that this goal may be achieved by focusing future work on the A3AR pathway, in particular, as its activation provides robust pain reduction across several types of pain."

Researchers are excited to note that A3AR agonists are already in advanced clinical trials as anti-inflammatory and anticancer agents and show good safety profiles. "These studies suggest that A3AR activation by highly selective small molecular weight A3AR agonists such as MRS5698 activates a pain-reducing pathway supporting the idea that we could develop A3AR agonists as possible new therapeutics to treat chronic pain," Salvemini said.

We rushed her, head wrapped like a tiny mummy, to the medical center at MIT, where we generally go for pediatric care. Julia wept while the nurse cleaned and examined her lacerated skin. After a short exam, she sent us to the emergency department at Children's Hospital Boston for stitches. "How bad is that, generally?" I asked, having never experienced suturing either for myself or my cautious, risk-averse, older daughter.

"It can be traumatic," the nurse said.

Julia cried, "I don't want stitches."

It's a large needle, but Julia is too busy coloring to notice.

So I braced myself for the worst: an endless wait and nerve-wracking bustle; screaming, germ-laden children and brusque, end-of-shift staff. But more than anything, I dreaded the inevitable pain in store for my small child with the deep cut.

(I know, kids get banged up on the path to adulthood and some pain is unavoidable. Still, when bloody heads are involved, I tend to overreact.)

Indeed, I was in full Mama Bear mode when into our exam room strode Dr. Baruch Krauss, the attending physician that evening.

Dark, lean and intense, Dr. Krauss shook my hand and then went straight to Julia, complimenting her pink, sparkly shoes. She lit up and was eager to chat. They talked about exactly how old she was (nearly six-and-three-quarters) and what she likes to do (climb trees). Then he gently rubbed a bit of Novocaine gel on her cut and said he'd be back.

Five times over the next 40 minutes or so, Krauss came in and re-applied the anesthetic, gently squeezing the site with his thumb and forefinger. Why, I wasn't sure. Was it a dosing thing? Was he just numbing the wound even more before the scary stitching began? With each visit, he engaged Julia to learn something new about her. For instance, she loves to draw.

And, she loves snacks. On my way back from the cafe with treats, Krauss stopped me in the hall and said something like, "I'm going to stitch her up; it really won't be bad." I rolled my eyes. But, he added, "I need you to work with me. I'm going to give you a task." Fine, I said, though the whole thing sounded a little gimmicky.

Krauss returned with an oversized 101 Dalmations coloring book and a handful of Magic Markers. He opened to a page overflowing with dog outlines. "Julia," he said. "I want you to color each dog's ear a different color, OK? Which color do you want to start with?"

Saturday, November 22, 2014

Neuropathic pain is pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. Despite the availability of many effective drugs and guidelines for the treatment of neuropathic pain, evidence from the United States and Europe suggests that they are not widely used, and many cases remain under- or untreated. Our goal through the global year campaign is to raise awareness of issues surrounding neuropathic pain.